Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZM5VMX)

• DOT Name: Protein mab-21-like 2 (MAB21L2)
• Gene Name: MAB21L2
• Related Disease:
  Colobomatous microphthalmia-rhizomelic dysplasia syndrome
  Microphthalmia
  Osteochondrodysplasia
  Skeletal dysplasia
  Coloboma
  Osteoporosis
  Intellectual disability
  Rheumatoid arthritis
• UniProt ID: MB212_HUMAN
• Pfam ID: PF03281 ; PF20266
• Sequence:
  MIAAQAKLVYQLNKYYTERCQARKAAIAKTIREVCKVVSDVLKEVEVQEPRFISSLSEID
  ARYEGLEVISPTEFEVVLYLNQMGVFNFVDDGSLPGCAVLKLSDGRKRSMSLWVEFITAS
  GYLSARKIRSRFQTLVAQAVDKCSYRDVVKMIADTSEVKLRIRERYVVQITPAFKCTGIW
  PRSAAQWPMPHIPWPGPNRVAEVKAEGFNLLSKECYSLTGKQSSAESDAWVLQFGEAENR
  LLMGGCRNKCLSVLKTLRDRHLELPGQPLNNYHMKTLLLYECEKHPRETDWDESCLGDRL
  NGILLQLISCLQCRRCPHYFLPNLDLFQGKPHSALESAAKQTWRLAREILTNPKSLDKL
• Function: Required for several aspects of embryonic development including normal development of the eye.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colobomatous microphthalmia-rhizomelic dysplasia syndrome	DISXGM26	Definitive	Autosomal dominant	[1]
Microphthalmia	DISGEBES	Definitive	Biomarker	[2]
Osteochondrodysplasia	DIS9SPWW	Definitive	Biomarker	[3]
Skeletal dysplasia	DIS5Z8U6	Definitive	Biomarker	[3]
Coloboma	DISP39N5	Strong	Biomarker	[2]
Osteoporosis	DISF2JE0	Strong	Altered Expression	[4]
Intellectual disability	DISMBNXP	Limited	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[5]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein mab-21-like 2 (MAB21L2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein mab-21-like 2 (MAB21L2).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein mab-21-like 2 (MAB21L2).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Protein mab-21-like 2 (MAB21L2).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Protein mab-21-like 2 (MAB21L2).	[10]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Protein mab-21-like 2 (MAB21L2).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein mab-21-like 2 (MAB21L2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein mab-21-like 2 (MAB21L2).	[12]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Zebrafish mab21l2 mutants possess severe defects in optic cup morphogenesis, lens and cornea development.Dev Dyn. 2019 Jul;248(7):514-529. doi: 10.1002/dvdy.44. Epub 2019 May 21.
• [3] Generation and characterization of pathogenic Mab21l2(R51C) mouse model.Genesis. 2018 Dec;56(11-12):e23261. doi: 10.1002/dvg.23261. Epub 2018 Nov 29.
• [4] The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors.PLoS One. 2012;7(9):e45142. doi: 10.1371/journal.pone.0045142. Epub 2012 Sep 24.
• [5] Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast cells: correlates with disease activity.Genes Immun. 2007 Sep;8(6):480-91. doi: 10.1038/sj.gene.6364400. Epub 2007 Jun 14.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.